S295: CLINICAL RELEVANCE OF SPLEEN VOLUME AND PLATELET COUNT WITH BLEEDING EVENTS IN PATIENTS WITH ACID SPHINGOMYELINASE DEFICIENCY (ASMD)
Authors: M. Fournier, J. Msihid, A. Willemze, F. Laredo, R. Pulikottil-Jacob
Journal: HemaSphere (2022)

Background: Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare, lysosomal storage disease with a broad spectrum of clinical manifestations. Within that spectrum, ASMD type B and type A/B are often referred to as chronic ASMD. In Type 1 Gaucher disease, increased bleeding tendency is attributed to thrombocytopenia secondary to hypersplenism and/or bone marrow infiltration noticed in patients with splenomegaly and thrombocytopenia. However, ASMD patients have a bleeding tendency that is not proportionally attributed to any association or explanation; hence further research is needed to study the cause of bleeding among patients with ASMD. Aims: To characterize the association between bleeding events (BE), spleen volume (SV), and platelet count by retrospectively analyzing data from a previously published prospective, multicenter, longitudinal study (MSC12840 [SPHINGO-001-00]) in patients with chronic ASMD (N=59; age: 7–64 years; 30 were < 18 years; male: 53%; up to 3 visits per patient with 6–11 years follow-up, 2001–2012). Methods: This study retrospectively screened medical charts of 59 adults and pediatrics for BE specified under the hematopoietic body system and their respective SV and platelet count. SV (in multiple of normal, MN) and platelet count (in 103/UL) were measured at baseline, year 1, and end of study [median years of observation (range), 10.2 years (4.7–11.1)]. As reported in the medical history captured at each visit, BE were selected with a series of keywords indicating hemorrhage, bleed, or transfusion post-medical review. To characterize their association with BE, SV and platelet counts were considered at the visit prior to the observation of the event. A general linear mixed model was performed using SV as a continuous or a class variable (<6, 6–15, and >15 MN). The associations between platelet counts (below 100 x 103/UL) and SV were also explored. Results: Overall, 59 patients were enrolled, 50 patients completed year 1 visit, and 32 patients completed the final visit (9 died, 9 discontinued, and 9 were lost to follow-up). Twenty-six patients reported BE across the two observed periods, i.e., baseline to 1 year and 1 year to final study visit. No BE was reported with SV <6 MN at any period; however, there was a trend for a higher event rate in patients with higher SV, per visit (Table 1). A higher SV of +5 MN or +10 MN was associated with a 1.8-times (odds ratio [95% confidence interval]: 1.85 [1.05, 3.29]) and 3.4-times (3.45 [1.10, 10.82]) increased risk of BE, respectively. Severe splenomegaly (>15 MN) was associated with a higher and non-significant risk of BE vs. moderate splenomegaly (6–15 MN; 2.54 [0.58, 11.08]). In addition, patients with low platelet counts (<100 x 103/UL) had higher SV, per visit (Table 1). The p-value for the chi-square test for association between platelet count and SV across visits was 0.006; it was 0.058, 0.127, and 0.302 at baseline, year 1, and end of the study, respectively. There was a moderate negative correlation (r = –0.47) between platelet count and SV across visits. Image:Summary/Conclusion: This analysis highlighted the association between SV and BE among patients with chronic ASMD. Since a statistically significant association between SV and thrombocytopenia was observed across visits, hypersplenism appears to be a contributor for the pathophysiology of bleedings among these patients. These associations help better understand the clinical relevance of SV measurements in ASMD. Prospective validation is warranted to confirm the results of these analyses.